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A Phase I Study of Subcutaneous "CYT 107" (Interleukin-7) in Refractory Metastatic Melanoma or Renal Cell Carcinoma

Phase 1
18 Years
Not Enrolling
Kidney Cancer, Melanoma (Skin)

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Trial Information

A Phase I Study of Subcutaneous "CYT 107" (Interleukin-7) in Refractory Metastatic Melanoma or Renal Cell Carcinoma



- Determine the safety of recombinant interleukin-7 (IL-7) in patients with metastatic
melanoma or locally advanced or metastatic renal cell carcinoma.

- Confirm the previously documented safety profile of non-glycosylated IL-7 in these

- Determine the safety of higher doses of recombinant IL-7 in these patients.

- Determine the maximum tolerated dose of recombinant IL-7 in these patients.

- Determine the biologically active dose of recombinant IL-7 in these patients.


- Determine the pharmacokinetics and pharmacodynamics of recombinant IL-7 in these

- Compare the biological and clinical effects of recombinant IL-7 with non-glycosylated
IL-7 in these patients.

- Determine the potential antitumor effect of recombinant IL-7 in these patients.

- Determine the dose and administration schedule of recombinant IL-7 in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to lymphocyte
count (normal lymphocyte count [CD4+ T cells > 400/mm^3] vs lymphopenic [CD4+ T cells <
400/mm^3]). Patients are assigned to 1 of 2 treatment groups.

- Group 1 (normal lymphocyte count): Patients receive recombinant interleukin-7 (IL-7)
subcutaneously once a week (to determine an active dose) for up to 3 weeks in the
absence of disease progression or unacceptable toxicity.

- Group 2 (lymphopenic): Patients receive recombinant IL-7 subcutaneously once a week for
up to 3 weeks at one dose level below the active dose determined in group 1.

Cohorts of 3-6 patients from each group receive escalating doses of recombinant IL-7 until
the maximum tolerated dose (MTD) is determined. The MTD is the defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 30
additional patients may be treated at the MTD.

Patients undergo blood and bone marrow collection periodically for pharmacokinetic,
pharmacodynamic, and immunological studies. Samples are analyzed for the presence of
antibodies and proteins via ELISA; CD3, CD4, and CD8 T cell counts, CD127, Ki-67, and Bcl-2
expression in CD4+ and CD8+ T cells, and CD19 B cell counts via flow cytometry; and clonal B
cell proliferation via PCR and flow cytometry.

After completion of study treatment, patients are followed at 3 months.

Inclusion Criteria


- Histologically confirmed diagnosis of 1 of the following:

- Melanoma

- Metastatic disease

- Renal cell carcinoma

- Locally advanced and unresectable disease OR metastatic disease

- Refractory to standard therapy OR ineligible to receive standard therapy

- Measurable or evaluable disease

- Previously received high-dose interleukin-2 OR have a contraindication for this

- No previously untreated or unstable brain metastases

- No splenic metastasis


- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count > 1,000/mm^3

- Platelet count > 100,000/mm^3

- PT/PTT ≤ 1.5 times upper limit of normal (ULN)

- Creatinine < 1.5 times ULN

- AST and ALT < 2.5 times ULN

- Conjugated (Direct) bilirubin ≤ 1.25 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- LVEF ≥ 45% by cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine
echocardiogram, or other stress test) for patients meeting any of the following

- History of ECG abnormalities

- Symptoms of cardiac ischemia

- At least 50 years of age and over

- Familial or personal history of heart failure

- Previously treated with antimitotic agents susceptible to trigger heart failure

- FEV_1 > 60% of predicted (for patients with a prolonged smoking history or symptoms
of respiratory dysfunction)

- No concurrent cognitive impairment or likelihood of developing cognitive impairment
on study therapy

- No concurrent splenomegaly or proliferative hematologic disease

- No documented HIV positivity

- No acute hepatitis A or hepatitis B or C

- Positive hepatitis B serology indicative of previous immunization (i.e., HBs Ab
positive and HBc Ab negative) allowed

- Positive hepatitis C serology allowed provided HCV RNA load by PCR is negative

- Resting blood pressure ≤ 140/90 mm Hg on standard antihypertensive therapy

- Untreated hypertensive patients who received standard antihypertensive therapy
allowed provided hypertension is well controlled

- No QTc prolongation ≥ 470 msec

- No prior history of cardiovascular disease, arrhythmias, or significant ECG

- No active infection requiring systemic treatment and/or hospitalization within the
past 28 days

- Patients who have completed therapy or are clinically stable on therapy, in the
opinion of the investigator, are eligible

- No history of autoimmune disease

- No history of severe asthma

- No history of medical or psychiatric disease that would preclude study treatment

- No documented cirrhosis or documented acute hepatitis


- See Disease Characteristics

- More than 2 weeks since prior systemic corticosteroid therapy

- More than 4 weeks since prior and no other concurrent cytotoxic therapy,
immunotherapy, biological agents (i.e., cytokines, growth factors, or monoclonal
antibodies), or antitumor vaccines

- More than 7 days since prior hepatotoxic drugs unless medically necessary

- More than 2 days since prior alcohol consumption

- More than 1 day since prior acetaminophen use

- No prior splenectomy

- No prior allogeneic hematopoietic stem cell transplantation or solid organ

- No concurrent palliative therapy

- No concurrent chemotherapy

- No concurrent chronic anticoagulation (i.e., high-dose warfarin or heparin)

- Warfarin dose 1 to 2 mg/day allowed

- No concurrent chronic medications for asthma

- No other concurrent investigational agents

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of recombinant interleukin-7 (IL-7)

Safety Issue:


Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

December 2010

Related Keywords:

  • Kidney Cancer
  • Melanoma (Skin)
  • recurrent renal cell cancer
  • stage IV renal cell cancer
  • stage III renal cell cancer
  • recurrent melanoma
  • stage IV melanoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Melanoma



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182